Stewart D J, Verma S, Maroun J A
Ontario Cancer Treatment and Research Foundation, Ottawa Regional Cancer Centre, Canada.
Am J Clin Oncol. 1987 Dec;10(6):517-9. doi: 10.1097/00000421-198712000-00012.
In light of preclinical evidence that disulfiram and related compounds decrease the toxicity and increase the therapeutic index of cisplatin, 12 patients were treated with a combination of cisplatin and oral disulfiram to determine the maximum tolerated dose of disulfiram that could be combined with cisplatin 100 mg/m2, and to determine the dose-limiting toxicity of disulfiram in this combination. Reversible confusion was the dose-limiting toxicity at a disulfiram dose of 3,000 mg/m2 administered 1 h before the end of a 2-h cisplatin infusion. A randomized study of cisplatin with or without disulfiram 2,000 mg/m2 p.o. is currently being conducted to determine the effect of disulfiram on cisplatin toxicity and pharmacology.
鉴于临床前证据表明双硫仑及相关化合物可降低顺铂的毒性并提高其治疗指数，对12例患者采用顺铂与口服双硫仑联合治疗，以确定可与100mg/m²顺铂联合使用的双硫仑最大耐受剂量，并确定该联合用药中双硫仑的剂量限制性毒性。在2小时顺铂输注结束前1小时给予3000mg/m²双硫仑时，可逆性意识模糊是剂量限制性毒性。目前正在进行一项随机研究，比较顺铂联合或不联合口服2000mg/m²双硫仑的疗效，以确定双硫仑对顺铂毒性和药理学的影响。
